H.T. Eich

Role of [18F]-fluoro-2-deoxy-D-glucose positron emission tomography in early and late therapy assessment of patients with advanced Hodgkin lymphoma treated with bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine and prednisone.

Abstract The prognostic value of positron emission tomography (PET) in early therapy response assessment, after completion of chemotherapy and 3 months after the end of treatment in advanced Hodgkin lymphoma (HL) remains to be defined. We report the results of 69 patients with first presentation of advanced HL. [18F]-fluoro-2-deoxy-d-glucose (FDG)-PET scan was performed after four cycles (PET-4), on completion of chemotherapy after 6/8 cycles (PET-6/8) and 3 months after the completion of chemotherapy (PET 3-months). Median follow-up was 55 months. The negative predictive value (NPV) for PET-4, PET-6/8 and PET 3-months was 98%, 95% and 97%, respectively. The 4-year progression-free survival (PFS) for PET-4 negative (n = 51) and PET-4 positive (n = 18) patients was 96% and 78%, respectively (p = 0.016). The 4-year PFS for PET-6/8 negative (n = 59) and PET-6/8 positive (n = 9) patients was 95% and 78%, respectively (p = 0.046). Patients with a large mediastinal mass constituted nearly all of the PET-4 positive (16/18) and PET-6/8 positive (8/9) patients. After radiotherapy of PET-6/8 positive patients, PET 3-months was negative in 64 (97%) and positive in two (3%) patients. PET 3-months after the end of chemotherapy was of limited value when the interim PET-4 was negative. Interim PET after four cycles of bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine and prednisone (BEACOPP) is a strong prognostic marker for PFS in advanced HL.

Assessment of Tumor Size Reduction Improves Outcome Prediction of Positron Emission Tomography/Computed Tomography After Chemotherapy in Advanced-Stage Hodgkin Lymphoma

PURPOSE Positron emission tomography (PET) after chemotherapy can guide consolidating radiotherapy in advanced-stage Hodgkin lymphoma (HL). This analysis aims to improve outcome prediction by integrating additional criteria derived by computed tomography (CT). PATIENTS AND METHODS The analysis set consisted of 739 patients with residues≥2.5 cm after chemotherapy from a total of 2,126 patients treated in the HD15 trial (HD15 for advanced stage Hodgkins disease: Quality assurance protocol for reduction of toxicity and the prognostic relevance of fluorodeoxyglucose-positron-emission tomography [FDG-PET] in the first-line treatment of advanced-stage Hodgkins disease) performed by the German Hodgkin Study Group. A central panel performed image analysis and interpretation of CT scans before and after chemotherapy as well as PET scans after chemotherapy. Prognosis was evaluated by using progression-free survival (PFS); groups were compared with the log-rank test. Potential prognostic factors were investigated by using receiver operating characteristic analysis and logistic regression. RESULTS In all, 548 (74%) of 739 patients had PET-negative residues after chemotherapy; these patients did not receive additional radiotherapy and showed a 4-year PFS of 91.5%. The 191 PET-positive patients (26%) receiving additional radiotherapy had a 4-year PFS of 86.1% (P=.022). CT alone did not allow further separation of patients in partial remission by risk of recurrence (P=.9). In the subgroup of the 54 PET-positive patients with a relative reduction of less than 40%, the risk of progression or relapse within the first year was 23.1% compared with 5.3% for patients with a larger reduction (difference, 17.9%; 95% CI, 5.8% to 30%). CONCLUSION Patients with HL who have PET-positive residual disease after chemotherapy and poor tumor shrinkage are at high risk of progression or relapse.

Neoadjuvant radiochemotherapy and surgery for advanced rectal cancer : prognostic significance of tumor regression.

Purpose:Preoperative radiochemotherapy is widely used in the treatment of locally advanced rectal cancer. The predictive value of response to neoadjuvant treatment remains uncertain. We retrospectively evaluated the impact of downstaging and tumor regression as prognostic factors and its influence on the ability to perform sphincter-sparing surgery.Patients and Methods:A total of 72 consecutive patients with advanced rectal cancer were included in this retrospective analysis. All patients were treated with preoperative 5-fluorouracil-based chemotherapy and pelvic radiation with a total dose of 50.4 Gy followed by surgery 6 weeks later.Results:A sphincter-preserving procedure could be performed on 42 patients, and in all 72 patients complete resection (R0) was achieved. A pathological complete response (ypT0, ypN0) was achieved in 8 (11%) patients. None of the patients showing a complete pathological response relapsed or died during the follow-up period. At a median follow-up of 28 months, 65 patients were alive, none of these patients had local recurrence and 15 patients had metastatic disease. Patients showing a complete pathological response had a significantly better 2-year disease-free survival compared to patients with ≥10% residual tumor cells (p = 0.024). Patients < 65 years showed a significantly better response rate, compared with those > 65 years of age (p = 0.036). Acute toxicity was moderate.Conclusion:Preoperative radiochemotherapy is an effective and safe treatment for patients with locally advanced rectal cancer. Pathological parameters after preoperative radiochemotherapy, including tumor regression grading, could be correlated with disease-free survival. The impact of tumor regression grading needs to be further validated in prospective clinical trials.Hintergrund:Die präoperative Radiochemotherapie (RChT) gefolgt von einer Operation stellt heute die Standardbehandlung für Patienten mit lokal fortgeschrittenem Rektumkarzinom dar. Der Vorhersagewert des Ansprechens auf eine neoadjuvante RChT ist nicht definiert. Wir untersuchten retrospektiv die Bedeutung des Tumoransprechens (Downstaging) und der Tumorregression als prognostische Faktoren und ihren Einfluss, eine sphinktererhaltende Operation zu ermöglichen.Material und Methode:Die vorliegende Analyse umfasst 72 konsekutive Patienten mit fortgeschrittenen Rektumkarzinomen, die im Zeitraum Januar 1999 bis Dezember 2006 eine neoadjuvante RChT erhielten. Die Behandlung bestand aus einer perkutanen Radiotherapie mit 50,4 Gy und einer simultanen 24-h-Dauerinfusion von 5-Fluorouracil (Woche 1 und 5) gefolgt von einer radikalen Tumorresektion. Neben dem Ansprechen des Tumors im Sinne eines Downstagings wurden mögliche prognostische Faktoren analysiert.Ergebnisse:Nach einer medianen Nachbeobachtungszeit von 28 Monaten kam es bei keinem Patienten zu einem Lokalrezidiv und bei allen 72 Patienten gelang eine komplette Resektion (R0). Das Ansprechen auf die neoadjuvante RChT im Sinne einer histopathologischen Tumorregression konnte als relevanter Prognosefaktor für das krankheitsfreie Überleben herausgearbeitet werden (Abbildung 1). 8 Patienten (11%) erreichten eine histopathologische komplette Remission (ypT0, ypN0). Darüber hinaus zeigten Patienten unter 65 Jahre ein signifikant besseres Ansprechen auf die präoperative RChT im Sinne eines Downstagings als Patienten über 65 Jahre (p = 0,036). Die Akuttoxizität der neoadjuvanten Therapie ist moderat.Schlussfolgerung:Die neoadjuvante RChT mit anschließender radikaler Resektion ist eine effektive und sichere Behandlung lokal fortgeschrittener Rektumkarzinome. Die Tumorregression konnte mit dem krankheitsfreien Überleben korreliert werden. Inwieweit die Tumorregression als valider Prognoseparameter angesehen werden kann, muss in prospektiven klinischen Studien überprüft werden.

Impact of risk factors on outcomes in early-stage Hodgkin's lymphoma: an analysis of international staging definitions

BACKGROUND In early-stage Hodgkins lymphoma (HL), treatment according to the early favorable or unfavorable subgroup is guided by staging definitions, which differ between various study groups worldwide. We analyzed risk factors used in different international staging systems and their impact on the outcome of early-stage HL patients. PATIENTS AND METHODS In 1173 early-stage HL patients treated homogenously within the German Hodgkin Study Group (GHSG) trials HD10 and HD11, the impact of three staging systems developed and used by the GHSG, the European Organization for Research and Treatment of Cancer (EORTC), and the National Comprehensive Cancer Network (NCCN) in discriminating risk groups for progression-free survival (PFS) and overall survival (OS) was assessed and the relevance of their single risk factors was investigated. RESULTS All the three staging systems defined an unfavorable risk group out of early-stage patients of comparable size (56%, 55%, and 57%), having a significantly poorer PFS and OS as compared with the corresponding favorable group; 5-year differences between early favorable and early unfavorable in terms of PFS were 9.4% (HR 2.61, 95% CI 1.74-3.91), 6.7% (HR 2.10, 95% CI 1.41-3.13), and 8.6% (HR 2.14, 95% CI 1.45-3.16) with the GHSG, EORTC, and NCCN definition, respectively. Sensitivity was high for all systems (84%, 79%, and 83%); however, there was a low specificity with high rates of false-positive results (1-specificity 54%, 53%, and 55%, respectively). Models of high sensitivity included risk factors associated with large tumor burden and high tumor activity. Most risk factors for tumor-specific end points were also predictive of OS. CONCLUSIONS Differentiating between a favorable and an unfavorable risk group has significant impact on PFS and OS in early-stage HL patients in the modern treatment era. Risk-adapted treatment strategies using new risk factors with higher specificity are needed.

Radiotherapy of splenomegaly : a palliative treatment option for a benign phenomenon in malignant diseases.

Purpose:Since the 20th century, radiotherapy (RT) has been used for treatment of symptomatic splenomegaly (SM). SM occurs in association with hematologic disorders. The purpose of this analysis was to determine the indication, treatment concepts, and efficiency of RT.Material and Methods: Clinical features, treatment concepts, and outcome data during the past 20 years were analyzed. Endpoints were pain relief, symptomatic and hematological response, and treatment-related side effects.Results:From 1989–2009, a total of 122 patients received 246 RT courses because of symptomatic SM. Overall 31 patients had chronic myelogenous leukemia (CML), 37 had chronic lymphocytic leukemia (CLL), 23 had osteomyelofibrosis (OMF), 17 had polycythemia vera (PV), 5 had acute myelogenous leukemia, 4 had idiopathic thrombocytopenic purpura (ITP), 3 had non-Hodgkin lymphoma (NHL), and 2 had multiple myeloma (MM). Patients were treated with 60Co gamma rays or 5–15MV photons. The fraction size ranged from 10–200 cGy and the total dose per treatment course from 30–1600 cGy. Significant pain relief was achieved for 74.8% of the RT courses given for splenic pain. At least 50% regression was attained for 77% of the RT courses given for SM. 36 patients died within 2 months due to the terminal nature of their disease. Of the RT courses applied for cytopenia, 73.6% achieved a significant improvement of hematological parameters and reduction of transfusion need. Notable hematologic toxicities were reported < EORTC/RTOG II°.Conclusion:The present analysis documents the efficacy of RT. In addition, RT as a palliative treatment option for symptomatic SM should not be forgotten.Einleitung:Seit Beginn des 20. Jahrhunderts hat die Radiotherapie (RT) ihren festen Stellenwert in der Behandlung einer symptomatischen Splenomegalie (SM). Die SM tritt bei hämatologischen Erkrankungen auf. Klinisch stehen Kapselschmerz sowie eine Zytopenie im Vordergrund. Die vorliegende Analyse untersucht Indikation, RT-Konzepte und die Effektivität der RT.Material und Methode:Patientendaten der letzten 20 Jahre wurden hinsichtlich klinischer Angaben, RT-Konzepte und Ergebnisse evaluiert. Endpunkte waren Schmerzfreiheit, hämatologisches Ansprechen nach RT sowie therapieassoziierte Nebenwirkungen.Ergebnisse:Zwischen 1989 und 2009 wurden 122 Patienten (79 Männer und 43 Frauen) mit insgesamt 246 RT-Serien behandelt. Folgende Grunderkrankungen waren Ursache für die Splenomegalie: CML (31), CLL (37), Osteomyelofibrose, (23), Polycyt haemia vera (17), AML (5), idiopathische Thrombozytopenie (4), Non-Hodgkin-Lymphom (3) und Plasmozytom (2) (Tabelle1). Die Behandlung erfolgte am Telekobalttherapiegerät oder am Linearbeschleuniger (5–15 MeV Photonen). Es wurden Einzelreferenzdosen zwischen 0,1–2 Gy und Gesamtreferenzdosen zwischen 3–16 Gy appliziert (Tabelle 2). Bei 74,8% der RT-Serien (74,8%), die aufgrund einer schmerzhaften Splenomegalie durchgeführt wurden, konnte eine Schmerzlinderung erzielt werden. Bei 77% der RT-Serien kam es zu einer Verkleinerung der Milz um bis zu 50% (Abbildung 1). 36 Patienten verstarben weniger als 2 Monaten nach Abschluss der RT im Rahmen der infausten Prognose ihrer Grunderkrankung. Bei 73,6% der RT-Serien kam es zu einer Verbesserung hinsichtlich Thrombozytopenien und die Transfusionsfrequenz nahm ab (Tabelle 3). Es wurden lediglich hämatologische Toxizitäten < II° (EORTC/RTOG) beobachtet.Schlussfolgerung:Die vorliegende Analyse belegt die hohe Effektivität der RT bei geringem Nebenwirkungsspektrum. Die RT der symptomatischen Splenomegalie sollte als wirksame palliative Option nicht in Vergessenheit geraten.

The significance of radiation therapy for symptomatic vertebral hemangiomas (SVH)

PURPOSE To evaluate the efficacy of radiation therapy (RT) for symptomatic vertebral hemangioma (SVH). MATERIAL AND METHODS Based on the Registry for Rare Benign Disorders (RRBD) of the German Cooperative Group on Radiation Therapy for Benign Diseases (GCG-BD), the clinical information, treatment plans and outcome data from seven cooperating German RT institutions were analyzed retrospectively. RESULTS Over a period of 39 years (1969-2008), a total of 84 patients with 96 symptomatic lesions underwent RT. The predominant indication was pain in 97.6%, and, in addition, 28.6% of patients had neurological deficits. The median total dose was 34 Gy (4.5-45 Gy), and the median single dose 2.0 Gy (0.5-3.0 Gy). After a median follow-up of 68 months (6-422 months), complete symptom relief (CR) occurred in 61.9% of patients, 28.6% had partial relief, and 9.5% had no relief (NR). The overall response rate (CR + PR) was 90.5%. In 26.2% of patients, radiologic signs of remineralization were noted. After a median follow-up of 70 months (8-124 months), symptom progression occurred in eight patients (9.5%). Therefore, the long-term rate of local control was 80.9%. Multivariate statistical analysis revealed a significantly higher rate of symptom relief and local control for total doses > or = 34 Gy. Side effects > RTOG/EORTC grade 2 were not observed. CONCLUSION RT is a safe and effective for treatment of SVH. Total doses of at least 34 Gy are recommended to achieve optimal treatment response.ZusammenfassungZiel:Analyse der Effektivität der Radiotherapie (RT) zur Behandlung symptomatischer Wirbelkörperhämangiome (sWKH).Material und Methodik:Basierend auf dem Register für seltene gutartige Erkrankungen der German Cooperative Group on Radiation Therapy for Benign Diseases (GCG-BD) wurden die klinischen Angaben, Behandlungstechniken und Ergebnisse aus sieben Zentren retrospektiv analysiert.Ergebnisse:Über eine Zeitspanne von 39 Jahren (1969–2008) wurden 84 Patienten mit insgesamt 96 symptomatischen Läsionen bestrahlt. Die Indikationsstellung zur RT erfolgte in 97,6% aufgrund von Schmerzen, 28,6% der Patienten hatten außerdem neurologische Defizite. Die mediane Gesamtdosis betrug 34 Gy (4,5–45 Gy), die mediane Einzeldosis 2,0 Gy (0,5–3,0 Gy). Nach einem medianen Nachbeobachtungszeitraum von 68 Monaten (6–422 Monate) hatten 61,9% eine komplette (CR), 28,6% eine partielle (PR) und 9,5% keine Symptomregression (NR). Die globale Ansprechrate (CR + PR) betrug somit 90,5%. In 26,2% der Patienten fanden sich radiologische Zeichen einer Remineralisation. Nach median 70 Monaten (8–124 Monate) entwickelten acht Patienten (9,5%) ein Rezidiv der klinischen Beschwerden, so dass die langfristige Kontrollrate 80,9% betrug. Die multivariate statistische Analyse zeigte für Gesamtdosen ≥ 34 Gy eine signifikant bessere Symptomregression und signifikant geringere Lokalrezidivrate. Nebenwirkungen > RTOG/EORTC-Grad 2 traten bei keinem der behandelten Falle auf.Schlussfolgerung:Die Strahlentherapie ist eine nebenwirkungsarme und effektive Therapieoption für die Behandlung von sWKH. Gesamtdosen von mindestens 34 Gy sind erforderlich, um ein optimales Ansprechen zu erzielen.AbstractPurpose:To evaluate the efficacy of radiation therapy (RT) for symptomatic vertebral hemangioma (SVH).Material and Methods:Based on the Registry for Rare Benign Disorders (RRBD) of the German Cooperative Group on Radiation Therapy for Benign Diseases (GCG-BD), the clinical information, treatment plans and outcome data from seven cooperating German RT institutions were analyzed retrospectively.Results:Over a period of 39 years (1969–2008), a total of 84 patients with 96 symptomatic lesions underwent RT. The predominant indication was pain in 97.6%, and, in addition, 28.6% of patients had neurological deficits. The median total dose was 34 Gy (4.5–45 Gy), and the median single dose 2.0 Gy (0.5–3.0 Gy). After a median follow-up of 68 months (6–422 months), complete symptom relief (CR) occurred in 61.9% of patients, 28.6% had partial relief, and 9.5% had no relief (NR). The overall response rate (CR + PR) was 90.5%. In 26.2% of patients, radiologic signs of remineralization were noted. After a median follow-up of 70 months (8–124 months), symptom progression occurred in eight patients (9.5%). Therefore, the long-term rate of local control was 80.9%. Multivariate statistical analysis revealed a significantly higher rate of symptom relief and local control for total doses ≥ 34 Gy. Side effects > RTOG/EORTC grade 2 were not observed.Conclusion:RT is a safe and effective for treatment of SVH. Total doses of at least 34 Gy are recommended to achieve optimal treatment response.

The German evidence-based guidelines for Hodgkin’s lymphoma@@@Die deutsche S3-Leitlinie für das Hodgkin-Lymphom: Aspects for radiation oncologists@@@Aspekte für Radioonkologen

This report reviews aspects of the German evidence-based guidelines for Hodgkin’s lymphoma relevant to radiation oncologists. Stage-adapted treatment is discussed with the focus on radiotherapy. Up-to-date literature citations provide an overview of current recommendations.ZusammenfassungDie vorliegende Analyse stellt wichtige strahlentherapeutische Aspekte der S3-Leitlinie für das Hodgkin-Lymphom zusammen. Diskutiert wird die stadiengerechte Behandlung mit dem Schwerpunkt Strahlentherapie. Die Auflistung der aktuellen Literatur gibt einen Überblick über derzeitige Empfehlungen.